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Discovery of a Potent Class of PI3Kα Inhibitors with Unique Binding Mode via Encoded Library Technology (ELT)
Hongfang Yang1, Patricia F Medeiros1, Kaushik Raha2
1MDR (Molecular Discovery Research) Boston, Platform Technology and Science, GlaxoSmithKline , 830 Winter Street, Waltham, Massachusetts 02451, United States.
Abstract:
In the search of PI3K p110α wild type and H1047R mutant selective small molecule leads, an encoded library technology (ELT) campaign against the desired target proteins was performed which led to the discovery of a selective chemotype for PI3K isoforms from a three-cycle DNA encoded library. An X-ray crystal structure of a representative inhibitor from this chemotype demonstrated a unique binding mode in the p110α protein.
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